DDT, heptachlor, and other chlorinated insecticides cause hepatocellular carcinomas and other neoplasias in rodents during life-time feeding tests. These findings are inconsistent with the facts that these compounds are not powerful alkylating agents, are not known to form covalent bonds with DNA, and are not mutagenic or are only weakly so in most of the in vitro and in vivo tests now available. Several hypotheses are advanced for their mechanisms of carcinogenic action. The most plausible of these is that they are metabolized in vivo to electrophilic compounds which combine with DNA to cause mutations which ultimately result in cellular transformations resulting in cancer. Although these metabolites are probably not highly reactive compared to other alkylating carcinogens, the parent compounds have very long residence times in human and animal tissues which could compensate for their relatively low reaction rates with metabolic substrates. During these studies, investigations would be made of the identification and site of formation of proximate and ultimate carcinogenic metabolites, identification of macromolecules which are altered as the result of their interactions with test compounds, and mechanisms of interaction between the test compounds and altered tissue constituents.